EGF receptor belongs to a family of erbB genes and its amplification and overexpression have been observed in a high percentage of primary human carcinomas of epithelial origin including cancers of the breast, colon, lung, head and neck, kidney, prostate and bladder, and played very important roles in cancer progression. It has been shown that anti-EGFR antibodies can block the binding of EGF to EGFR and the signal transduction in the cells, inhibit tumor progression in cancer patients. Several monoclonal anti-EGFR antibodies have proven effective in treatment of human patients in clinic. In 2005, Erbitux, a humanized mouse anti-EGFR monoclonal antibody was launched as the therapy for head and neck cancer by ImClone. In 2009, another humanized anti-EGFR monoclonal antibody was launched in China for the same indication by a Chinese Biopharmaceutical.
This invention is about the humanization of another mouse anti-EGFR monoclonal antibody, designed as clone LA22, which binds to different epitopes from the one recognized by Erbitux. It has been reported previously that once binds to the EGFR on the tumor cell surface, in the absence or presence of EGF, LA22 will internalize rather quickly, and can be an ideal candidate for antibody drug conjugate.